High cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) contents in mouse lung tumors

Mouse lung tumorigenesis is a convenient model for examining all stages of lung adenocarcinoma (AC) progression. Because enhanced cyclooxygenase 2 (CO X-2) expression has been observed in advanced human AC, we investigated the intracellular concentrations of the two cyclooxygenases, cyclooxygenase 1 (COX-1) and COX-2, at different times after carcinogen administration to A/ J mice. The concentrations of both proteins were much higher in urethane-in duced adenomas and carcinomas compared with control A/J mouse lung tissue ( P < 0.03 and P < 0.01 in adenomas and AC, respectively, for COX-1; P < 0.00 3 and P < 0.004 in adenomas and AC, respectively, for COX-2), Small benign tumors that arose spontaneously in 13-month-old mice also stained for COX-1 and COX-2, showing that this elevated enzyme content does not depend on ch emical induction. COX-1 and COX-2 immunostaining was observed in normal bro nchiolar and alveolar epithelia, alveolar macrophages and bronchiolar smoot h muscle, This is the first report of the cellular distribution of COX-1 an d COX-2 in murine lungs and the first in any species to demonstrate their c o-localization, COX content in isolated bronchiolar Clara cells, a putative cell of tumor origin, was equal to that found in tumors, suggesting that t he high enzyme content in neoplasms is due to their proportionally high con centration of these tumor precursor cells, Different patterns of COX-1 and COX-2 expression were observed in tumors of different growth patterns; only occasional small foci stained in solid adenomas, while most cells in papil lary adenomas were immunoreactive. This staining pattern was also seen in a denocarcinomas, but some of the papillary portions also included focally st ained and unstained regions. The continued expression during neoplastic pro gression of these specialized enzymes present in normal cells of tumor orig in suggests their function in maintenance of the neoplastic state.